Despite the recent attention to high rates of mental health problems including substance use disorders among the US veterans of the wars in Iraq and Afghanistan, most of the reports have been focused on excessive alcohol use and related problems. While clinicians are confronted with increasing reports of heavy and problematic marijuana use among the veterans, research on this drug and its association with affective disorders (e.g., post-traumatic stress disorder and major depressive disorder) is virtually nonexistent. There is a paucity of studies on the natural course of marijuana use and associated problems and there are no prospective studies on the comorbidity of cannabis use and affective disorders among veterans following deployment. The goal of this application is to conduct the first comprehensive prospective investigation of the trajectories of marijuana use, related problems, cannabis use disorders and concomitant affective disorders among 400 Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) veterans recruited from the Veterans Administration Medical Center post-deployment. The proposed longitudinal design is a particular strength in examining theoretically-determined predictors of change in marijuana use trajectories. Change (escalation and de-escalation over one year) and stability in marijuana use and abuse, alcohol, and other drug use disorders will be examined using latent transition analysis, and longitudinal associations will be examined using latent growth curve modeling. The proposed study will identify putative mechanisms (using marijuana for coping reasons) and investigate the moderating effects of individual differences (emotional vulnerability, cognitive, psychosocial, and physical/medical factors) that may explicate the relationship between negative affect (DSM-IV mood or anxiety disorder and/or state negative affectivity) and marijuana use/disorders. Using stratified sampling with proportional allocation, an equal proportion of frequent weekly marijuana users, past month users, infrequent past year users and non-users with lifetime history of marijuana use will be selected to allow for heterogeneity in examining longitudinal patterns of change in marijuana use. This study has the potential to yield information about the mechanisms that underlie the development of co morbidity and addictive disorders, a clinical problem that has substantial impact on public health due to increasing costs of addiction-related and mental health disability. Findings from this study will have wide-ranging implications for the assessment and treatment of OEF/OIF/OND veterans with co-occurring substance use and affective disorders and ultimately for providing them with a higher quality of life.